CHSâ„¢ - mode of action
Blood vessels present heparan sulphate at the interface towards blood, providing binding sites for antithrombin (AT). Such binding sites serve the purpose of enhancing the anticoagulant effect of AT, and hence the endothelial surface of the blood vessels is an active tissue that continuously interacts with the circulating blood.
When AT binds to the pentasaccharide sequence in heparin, a structural reorientation is induced in AT which implies that the thrombin binding site of AT becomes more readily available. This results in a thousand-fold increase of the inhibition rate without altering the stoichiometry. Once an irreversible AT-protease complex has been formed, the affinity between heparin and AT decreases and the complex may leave the surface and the immobilized heparin is ready to attract another AT molecule. This explains the catalytic role of heparin, which may occur both with soluble heparin, heparan sulphate and heparin adequately immobilized at a solid surface. It should be emphasized that CHS™ is not consumed in the process, but merely acts as a catalyst to potentiate the inhibitory capacity of AT.
